Attempts will be made to purify the insulin receptor of liver and fat cell membrane in sufficient quantity to permit detailed physical- chemical studies as well as crystallization for possible x-ray structural studies. Special emphasis will be given to the use affinity chromatography in the purification of peptide hormone receptors. Human placenta membranes will be used for solubilization and purification of insulin receptors. Detailed kinetics and the temprature dependence of particulate and detergent- solubilized adenylate cyclase activation by hormones will be studied. Inside-out cytoplasmic plasma membranes will be purified on lectin and hormone polymer columns. Affinity columns for adenylate cyclase will be prepared. The possible role of cyclic GMP in mediating metabolic effects of insulin and cholinergic drugs will be studied. The possible modulation of guanylate cyclase activity by hormones will be studied. Glucose transport carriers capable of being specifically phosphorylated will be characterized. Attempts will be made to synthesize special Beta-adrenergic drugs to directly measure receptors for catecholamines.